Review and meta-analysis of natural selection in mitochondrial complex I in metazoans
Bibliographic record
Abstract
Variation in mitochondrial DNA is often assumed to be neutral and is used to construct the genealogical relationships among populations and species. However, if extant variation is the result of episodes of positive selection, these genealogies may be incorrect, although this information itself may provide biologically and evolutionary meaningful information. In fact, positive Darwinian selection has been detected in the mitochondrial-encoded subunits that comprise complex I from diverse taxa with seemingly dissimilar bioenergetic life histories, but the functional implications of the selected sites are unknown. Complex I produces roughly 40% of the proton flux that is used to synthesize ATP from ADP, and a functional model based on the high-resolution structure of complex I described a unique biomechanical apparatus for proton translocation. We reported positive selection at sites in this apparatus during the evolution of Pacific salmon, and it appeared this was also the case in published reports from other taxa, but a comparison among studies was difficult because different statistical tests were used to detect selection and oftentimes, specific sites were not reported. Here we review the literature of positive selection in mitochondrial genomes, the statistical tests used to detect selection, and the structural and functional models that are currently available to study the physiological implications of selection. We then search for signatures of positive selection among the coding mitochondrial genomes of 237 species with a common set of tests and verify that the ND5 subunit of complex I is a repeated target of positive Darwinian selection in diverse taxa. We propose a novel hypothesis to explain the results based on their bioenergetic life histories and provide a guide for laboratory and field studies to test this hypothesis. Revision y Meta-analisis de Seleccion Natural en Complejo Mitochondrial I en Metazoans La variacion en el ADN mitocondrial se asume frecuentemente como neutral y es usada para construir las relaciones genealogicas entre poblaciones y especies. Sin embargo, si la variacion existente es el resultado de episodios de seleccion positiva, estas genealogias pueden ser incorrectas, aunque la informacion por si misma puede proveer informacion biologica y evolutiva relevante. De hecho, se ha detectado seleccion darwiniana positiva en subunidades mitocondriales codificantes que incluyen el complejo I de diversos taxa con historias bioenergeticas disimiles, aunque las implicancias funcionales de los sitios seleccionados son desconocidas. El complejo I produce aproximadamente el 40% del flujo de protones que es usado para sintetizar ATP a partir del ADP, y un modelo funcional basado en la estructura de alta resolucion el complejo I describio un aparato biomecanico unico para la translocacion de protones. Reportamos seleccion positiva en sitios de este aparato durante la evolucion del salmon del Pacifico, y aparentemente este fue el caso en publicaciones de otros taxa, pero la comparacion entre estudios resulta dificultosa debido al uso de diferentes analisis estadisticos para detectar seleccion y en muchos casos no se reportan sitios especificos. En el presente estudio, revisamos la bibliografia a cerca de la seleccion positiva en el genoma mitocondrial, los analisis estadisticos utilizados para la deteccion de la seleccion, asi como los modelos estructurales y funcionales disponibles actualmente para el estudio de las implicancias fisiologicas de la seleccion. Asimismo se realizo la busqueda de las huellas de la seleccion positiva entre los genomas mitocondriales codificantes de 237 especies con un set comun de analisis y se verifico que la subunidad ND5 del complejo I es un blanco repetido de seleccion positiva darwiniana en diversos taxa. Proponemos una novedosa hipotesis para explicar los resultados basados en la historia bioenergetica y proveemos una guia para estudios de laboratorio y campo para poner a prueba dichas hipotesis
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".